Equine Placentitis Update

What's the most common cause of late-term abortion in horses and remains challenging for veterinarians to diagnose and treat, despite ongoing research? If you said placentitis, you're right. To bring attendees of the 2013 Society for Theriogenology Conference, held Aug. 7-10 in Louisville, Ky., up to speed on the latest research on the complex topic, C. Scott Bailey, DVM, MS, Dipl. ACT, presented a review of placentitis diagnostics and treatments.

Placentitis—an inflammation of the placenta—is often caused by an ascending infection that enters the mare's uterus through the cervix. Bailey, an assistant professor of theriogenology at the North Carolina State University (NCSU) College of Veterinary Medicine, explained that placentitis is responsible for 10-40% of late-term abortions in mares; of those cases 60% are of the bacterial variety.

Clinical signs of placentitis often develop late in the course of disease and are generally nonspecific. Bailey said the most common clinical sign he encounters is premature udder development, and less commonly vulvar discharge. However, he noted, many cases simply present with late-term abortion or the birth of a sick or weak foal.

"Despite intense research and clinical focus, diagnosis for most forms of placentitis remains difficult and clinical treatment success remains limited."

Diagnostics

While early diagnosis would likely improve the chances of positive clinical outcomes, veterinarians are currently limited in their diagnostic options for placentitis.

Ultrasound Screening—Since the technique was introduced in 1997, ultrasound examination of the uterus and placenta has been the mainstay of placentitis diagnostics, Bailey said. Research indicates that the normal combined thickness of uterus and placenta (CTUP) for healthy mares less than 270 days of gestation is less than 7 millimeters (mm); mares ranging from 271 to 300 days of gestation should have a CTUP of less than 8 mm; mares between Days 301 and 330 should have a CTUP of less than 10 mm; and mares over 330 days should have a CTUP of less than 12 mm. Bailey said measurements above those normal ranges are clear indications of uterine pathology and suggestive of placentitis.

The challenge? "Frequent monitoring of mares with no known risk factors for placentitis represents a significant expense and may not be cost-effective or feasible," Bailey said.

Nonetheless, "At this time, ultrasonographic examination of the combined thickness of the uterus and placenta represents the most sensitive and specific diagnostic and screening tool that can be recommended for valuable or high-risk patients," he said.

Hormone Tests—Bailey said researchers have also explored the efficacy of measuring serum progestagen to diagnose or screen for placentitis. In mares with compromised pregnancies, he explained, previous research has shown that serum progestagen levels will either elevate prematurely (all mares' levels rise after 310 days of gestation) or drop severely, typically just before abortion.

"Prematurely rising progestagens are indicative of chronic stress to the foal, of which placentitis is by far the most common; falling progestagens indicate fetal demise and are not specific," he explained. "Elevated progestagen may occur at the same time as early thickening. Usually if progestagens are dropping quickly, treatment is too late."

SAA Tests—Finally, Bailey described recent research that explored the use of inflammatory blood protein levels to identify inflammation within the body. Specifically, researchers tested one inflammatory protein's (called serum amyloid A, or SAA) ability to identify mares with experimentally induced placentitis in late gestation. They found that mares' serum SAA levels rose significantly 48-144 hours after experimental infection, while control mares' SAA levels remained low, save for a short rise surrounding parturition.

"These findings warrant further work in clinical cases of naturally occurring placentitis to determine whether SAA may be used as an inexpensive, sensitive screening tool for placental function, and whether it is influenced by confounding factors such as extra-uterine disease or obesity," Bailey said.

He cautioned that SAA levels are not specific to placentitis—meaning any inflammation or infection within the body can cause those levels to rise—so veterinarians should interpret those results with caution.

Treatment

Traditionally veterinarians have used a combination of antibiotics, anti-inflammatory drugs, immune-modulatory medications, and progestins to treat placentitis. And recent research has been shedding light on which medications and treatment methods might be most effective.

Bailey described research showing that treating experimentally infected mares with a combination of trimethoprim sulfamethoxazole (TMS, a commonly used antibiotic), pentoxyfilline (PTX, a common anti-inflammatory), and altrenogest (ALT, a common progestin) yielded good results: 83% of those mares delivered viable foals, compared with no viable foals being born in the control group. Unfortunately, he said, those results haven't been replicated in clinical practice.

Additionally, he said, research from his laboratory showed that delaying placentitis treatment until CTUP measurements increase (as described previously) resulted in only 40% of mares delivering viable foals.

Bailey also reviewed some research regarding the different placentitis therapeutic options:

Antibiotics—Bailey said some of the common antibiotic agents used in placentitis treatment include TMS, cephalosporins, tetracyclines, sulfonamides, carboxypenicillins, and penicillin plus betalactamase inhibitors, all of which have been proven effective in controlling placentitis-causing bacteria in vitro (in the laboratory). He noted that researchers have learned much about the different drugs over the years:

Gentamicin, penicillin G, and TMS can all reach therapeutic concentrations in allantoic fluid (fluid in the chorioallantois, which is the outer layer of the placenta where the placenta and maternal uterus touch and exchange nutrients);

Penicillins are "highly effective" against Streptococcus zooepidemicus, one of the common bacteria found in mares with placentitis;

Gentamicin is effective against most of the Gram-negative bacteria that cause placentitis; and

Although TMS performs well in in vitro trials, the medication wasn't able to clear S. zooepidemicus from experimentally-infected mares' uteri.

"Hospitalized patients are generally treated with a combination of standard doses of penicillin G and gentamicin," Bailey said. "However, the need for repeated drug administration and catheter maintenance makes this combination impractical for prolonged therapy of patients maintained in a farm setting, and TMS is widely used for this purpose."

Anti-Inflammatory Drugs—Bailey said veterinarians often use flunixin meglumine (marketed as Banamine, a non-steroidal anti-inflammatory drug) in placentitis treatment, as previous research suggests it could help improve foal viability. Another study showed that it can help prevent prostaglandin synthesis and luteolysis, which would help a mare maintain pregnancy.

Veterinarians might also use pentoxyfilline in placentitis management. While its mechanism of action isn't well understood, Bailey said, it appears to help prolong the interval between placentitis infection and foaling when used in combination with TMS and ALT.

Bailey said researchers are also taking a closer look at whether treatment with glucocorticoids is effective in improving fetal viability in mares with placentitis.

Take-Home Message

Bailey said that while research on placentitis is ongoing, there are still many questions that remain to be answered.

"There is ongoing research at the Gluck Center in Kentucky, in our laboratory at NCSU, and in other laboratories, which have yielded interesting results, and we all hope that one or a combination of these findings will lead to improved treatment results," he concluded.

In the meantime, Bailey stressed that early disease detection is a key to successful treatment, and he encouraged horse owners and managers to contact their veterinarians quickly if they notice signs of disease, such as unusual mammary development or vaginal discharge.

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.